Phase 2 trial of ozuriftamab vedotin (BA3021), a conditionally binding ROR2-ADC, in patients with heavily pretreated squamous cell carcinoma of the head and neck.

6048 Background: Recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) represents a marked unmet need. ROR2 is a cell-surface transmembrane receptor protein tyrosine kinase highly expressed in several tumor types including HNSCC. Ozuriftamab vedotin is a conditionally binding ROR2 antibody-drug conjugate designed to reduce off-tumor toxicity and improve pharmacokinetics by conditionally binding to ROR2 under low-pH conditions (pH<6.7) of the tumor microenvironment, thus sparing normal tissue. This novel mechanism avoids tissue-mediated drug disposition and improves pharmacokinetics. The recommended Phase 2 dose of 1.8 mg/kg was determined from the Phase 1 trial (NCT03504488). Methods: This multi-center, open-label, single-arm Phase 2 trial evaluated ozuriftamab vedotin in patients (pts) with R/M SCCHN previously treated with anti-PD-1 agents. Patients with SCCHN were enrolled and received 1.8 mg/kg of ozuriftamab vedotin given in 2 schedules: once every two weeks (Q2W) or days 1 and 8 of a 21-day cycle (2Q3W). Tumor assessments were conducted by CT or MRI every 6 weeks from Cycle 1 Day 1 until week 12, then every 8 weeks up to 1 year. Evaluable pts included those with at least one post-treatment scan. ROR2 expression was characterized by immunohistochemistry. Additional assessments included pharmacokinetic, pharmacodynamic, immunogenicity, and biomarker evaluations to characterize efficacy and safety. Results: As of May 31, 2024, 31 pts received ozuriftamab vedotin either Q2W (n=12) or 2Q3W (n=19) for a median of 84 days. Pts had a median of 3 prior lines of therapy, and all had experienced failure of anti–PD-1 therapy. Among 28 evaluable pts (evaluable as defined as having complete 1 post dose tumor assessment) for best overall response, there were 10 responders (36%; 1 confirmed complete response, and 5 confirmed/4 unconfirmed partial responses, and 14 stable disease. A disease control rate of 86% was observed. Median duration of response for all confirmed responders has not been reached (>3.6 months; 95% CI, 0.4–NE). Most adverse events (AEs) were grade 1-2, with fatigue (59%), anemia (34%), and nausea (34%) being the most frequent. Six pts (19%) experienced grade 3 treatment-related AEs (TRAEs). Two pts experienced a grade 4 TRAE (1 pt with hyponatremia in 2Q3W cohort, and 1 pt with neuropathy in Q2W cohort). No grade 5 TRAEs were observed. Conclusions: Pts treated with ozuriftamab vedotin achieved a high rate of disease control with acceptable tolerability. Shows promising efficacy, including in pts refractory to anti-PD1 and warrants further evaluation in SCCHN. Clinical trial information: NCT03504488 .